A systematic review of the clinical features of pneumonia in children aged 5-9 years: Implications for guidelines and research

Background Childhood pneumonia presents a large global burden, though most data and guidelines focus on children less than 5 years old. Less information is available about the clinical presentation of pneumonia in children 5-9 years of age. Appropriate diagnostic and treatment algorithms may differ from those applied to younger children. This systematic literature review aimed to identify clinical features of pneumonia in children aged 5-9 years, with a focus on delineation from other age groups and comparison with existing WHO guidance for pneumonia in children less than 5 years old. Methods We searched MEDLINE, EMBASE and PubMed databases for publications that described clinical features of pneumonia in children 5-9 years old, from any country with no date restriction in English. The quality of included studies was evaluated using a modified Effective Public Health Project Practice (EPHPP) tool. Data relating to research context, study type, clinical features of pneumonia and comparisons with children less than 5 years old were extracted. For each clinical feature of pneumonia, we described mean percentage (95% confidence interval) of participants with this finding in terms of aetiology (all cause vs Mycoplasma pneumoniae), and method of diagnosis (radiological vs clinical). Results We included 15 publications, eight addressing all-cause pneumonia and seven addressing Mycoplasma pneumoniae. Cough and fever were common in children aged 5-9 years with pneumonia. Tachypnoea was documented in around half of patients. Dyspnoea/difficulty breathing and chest indrawing were present in approximately half of all-cause pneumonia cases, with no data on indrawing in the outpatient setting. Chest and abdominal pain were documented in around one third of cases of all-cause pneumonia, based on limited numbers. In addition to markers of pneumonia severity used in children <5 years, pallor has been identified as being associated with poorer outcomes alongside comorbidities and nutritional status. Conclusions Quality research exploring clinical features of pneumonia, treatment and outcomes in children aged 5-9 years using consistent inclusion criteria, definitions of features and age ranges are urgently needed to better inform practice and guidelines. Based on limited data fever and cough are common in this age group, but tachypnoea cannot be relied on for diagnosis. While waiting for better evidence, broader attention to features such as chest and abdominal pain, the role of chest radiographs for diagnosis in the absence of symptoms such as tachypnoea, and risk factors which may influence patient disposition (chest indrawing, pallor, nutritional status) warrant consideration by clinicians. Protocol registration PROSPERO: CRD42020213837.

Gordon et al [13] Macpherson et al [6] Othman et al [11] Sondergaard et al [14] Udomittipong et al a [12] Youn et al [19] Component B: Study Design -"Was the study described as randomized?" and related questions not applicable Component C: Confounders -Modified to, "Were important differences between groups described and considered in analyses?" A strong rating was given to a study that considered age, sex, ethnicity and comorbidities (unless cases with comorbid conditions were excluded). A moderate rating w given to a study that considered age, sex and comorbidities (unless cases with comorbid conditions were excluded). A weak rating was given to a study that did not consider at least age, sex and comorbidities (unless cases with comorbid conditions were excluded). Component B: Study Design -"Was the study described as randomized?" and related questions not applicable Component C: Confounders -Modified to, "Were important differences between groups described and considered in analyses?" A strong rating was given to a study that considered age, sex, ethnicity and comorbidities (unless cases with comorbid conditions were excluded). A moderate rating w given to a study that considered age, sex and comorbidities (unless cases with comorbid conditions were excluded). A weak rating was given to a study that did not consider at least age, sex and comorbidities (unless cases with comorbid conditions were excluded). Component D: Blinding -(Q1) modified to, "Was (were) the outcome assessor(s) aware of the research question?
-If data collection was by chart review, (Q2) was not applicable. If information was collected directly from patients or carers, (Q2) was applicable. Component B: Study Design -"Was the study described as randomized?" and related questions not applicable Component C: Confounders -Modified to, "Were important differences between groups described and considered in analyses?" A strong rating was given to a study that considered age, sex, ethnicity and comorbidities (unless cases with comorbid conditions were excluded). A moderate rating w given to a study that considered age, sex and comorbidities (unless cases with comorbid conditions were excluded). A weak rating was given to a study that did not consider at least age, sex and comorbidities (unless cases with comorbid conditions were excluded). The global rating of papers remained unchanged: 1. Strong = no weak ratings 2. Moderate = one weak rating 3. Weak = two or more weak ratings Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including h and each report retrieved, whether they worked independently, and if applicable, details of automation Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data fro independently, any processes for obtaining or confirming data from study investigators, and if applicab process.
Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatib study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide 10b List and define all other variables for which data were sought (e.g. participant and intervention characte assumptions made about any missing or unclear information. Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) study and whether they worked independently, and if applicable, details of automation tools used in the Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis

Synthesis methods
13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating t comparing against the planned groups for each synthesis (item #5)).
13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of m conversions.
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.
13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-ana model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software pack 13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. sub 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.

Reporting bias assessment
14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from re Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the s the review, ideally using a flow diagram.
16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why Study characteristics 17 Cite each included study and present its characteristics.

Risk of bias in studies
18 Present assessments of risk of bias for each included study.

Results of individual studies
19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) an (e.g. confidence/credible interval), ideally using structured tables or plots.

Results of syntheses
20a For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.
20b Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the s confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe t

Item # Checklist item
20c Present results of all investigations of possible causes of heterogeneity among study results.
20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized result Reporting biases 21 Present assessments of risk of bias due to missing results (arising from reporting biases) for each synt Certainty of evidence 22 Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed.

Discussion
23a Provide a general interpretation of the results in the context of other evidence.
23b Discuss any limitations of the evidence included in the review.
23c Discuss any limitations of the review processes used.
23d Discuss implications of the results for practice, policy, and future research.

OTHER INFORMATION
Registration and protocol 24a Provide registration information for the review, including register name and registration number, or stat 24b Indicate where the review protocol can be accessed, or state that a protocol was not prepared.
24c Describe and explain any amendments to information provided at registration or in the protocol. Support 25 Describe sources of financial or non-financial support for the review, and the role of the funders or spo Competing interests 26 Declare any competing interests of review authors.
Availability of data, code and other materials 27 Report which of the following are publicly available and where they can be found: template data collect studies; data used for all analyses; analytic code; any other materials used in the review.